Simultaneous evaluation of drug absorption and in vivo release behavior from coated mini tablets with Eudragit L 30 D-55 in rats using near-infrared imaging

We previously demonstrated the use of near-infrared (NIR) imaging to evaluate differences in disintegration for various capsule formulations after oral administration to rats. To further explore this techniques utility, in vitro and in vivo studies were conducted using mini tablets (2.5 mm in diameter and 2.17 mm in thickness) containing indocyanine green (ICG), acetaminophen (ACE), metoprolol tartrate (MET), and atenolol (ATE), prepared and coated with two different thicknesses of Eudragit® L 30 D-55. The in vitro results showed that the coated mini tablets exhibited acid resistance with slow leakage in acidic media and rapid release with a short lag time under neutral pH conditions as a function of coating thickness. Consistent with the in vitro dissolution profiles, oral drug absorption was also substantially affected by coating thickness. Although the AUC of ACE decreased only slightly, C_max decreased significantly, and T_max was prolonged with coating thickness increase. Similar trends in C_max and T_max were observed for MET and ATE; however, their AUCs decreased markedly with increasing coating thickness. ICG fluorescence intensity and area time profiles, which reflect the amount and extent of drug dissolved in the intestine, closely corresponded to the absorption profile of ACE quantified by deconvolution analysis, further suggesting distinct MET and ATE absorption characteristics. Collectively, these findings demonstrate that NIR imaging is a valuable tool for evaluating in vivo drug release from coated mini tablets.

Introduction